Public health efforts and current anti-obesity agents have not controlled the obesity epidemic. This disorder is increasingly prevalent in industrialized nations because of the abundance of food and the reduced activity levels that accompany the movement of populations from rural to urban settings. Obesity is loosely defined as an excess of body fat over that needed to maintain health.
Obesity is a condition in which excess body fat has accumulated to such an extent that health may be negatively affected. (World Health Organization (2000)). (Technical report series 894: Obesity: Preventing and managing the global epidemic). It is commonly defined as a Body Mass Index (BMI=weight divided by height squared) of 30 kg/m2 or higher. Overweight is distinguished and defined as a BMI between 25-29.9 kg/m2 (Obes Res. 1998 September; 6 Suppl 2:51S-209S. (Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults—The Evidence Report. National Institutes of Health).
Excessive body weight is associated with various diseases, particularly cardiovascular diseases, diabetes mellitus type 2, obstructive sleep apnea, certain types of cancer, and osteoarthritis (National Heart, Lung, and Blood Institute. Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults NIH Publication No. 98-4083 September 1998 National Institutes of Health). As a result, obesity has been found to reduce life expectancy. The primary treatment for obesity is dieting and physical exercise. If diet and exercise fails, anti-obesity drugs and bariatric surgery may be recommended in severe cases (National Institute for Health and Clinical Excellence. Clinical Guideline 43: Obesity: The prevention, identification, assessment and management of overweight and obesity in adults and children. London, 2006).
The pathogenesis of obesity is multi-factorial and includes the control of feeding behavior, mechanisms of fat storage, the components of energy intake and expenditure, and genetic and psychological influences. Likewise, the treatment of obesity is generally multi-factorial. Unfortunately, the mechanisms of fat storage and genetic influences are not, generally speaking, amenable to treatment. Moreover, the control of feeding behavior and psychological influences require prolonged treatment. Although the components of energy intake and expenditure are treatable, many obese individuals are resistant to or incapable of engaging in activities which significantly increase their energy expenditure. Therefore, controlling energy intake is an attractive approach for the treatment of obesity.
There is a need for new methods for managing weight and preventing or treating overweight and obesity. Further, treatments for obesity are typically no more effective in diabetic patients than in nondiabetic patients and are often less effective (see, for example: Baker et al., Met. Clin. Exper. 2012, 61:873; Scheen et al., Lancet 2006, 368:95489, 1660; Pi-Sunyer et al., J. Am. Med. Assoc. 2006, 295:7, 761; Khan et al., Obes. Res. 2000, 8:1, 43; Guare et al., Obes. Res. 1995, 3:4, 329; Wing et al., Diabetes Care 1987, 10:5, 563). Thus there is a need for weight loss agents and methods which are particularly effective in treating diabetic patients. In addition, there is a need for effective methods for weight loss in prediabetics and for improving their health even in the absence of weight loss, for example, converting prediabetics to nondiabetics.